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[FAT1在肺腺癌中的表达及其与免疫细胞浸润的关系]

[Expression of FAT1 in Lung Adenocarcinoma and Its Relationship 
with Immune Cell Infiltration].

作者信息

Ding Chen, Zhao Wenhao, Huang Hua, Li Yongwen, Zhang Zhanrui, Zhang Ruihao, Wang Yanan, Wu Di, Chen Chen, Liu Hongyu, Chen Jun

机构信息

Department of Thoracic Surgery, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi 832003, China.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.

出版信息

Zhongguo Fei Ai Za Zhi. 2024 Feb 20;27(2):109-117. doi: 10.3779/j.issn.1009-3419.2024.102.01.

DOI:10.3779/j.issn.1009-3419.2024.102.01
PMID:38453442
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10918241/
Abstract

BACKGROUND

Lung cancer is a leading cause of cancer-related deaths. Non-small cell lung cancer (NSCLC) is the most common pathological subtype, with adenocarcinoma being the predominant type. FAT atypical cadherin 1 (FAT1) is a receptor-like protein with a high frequency of mutations in lung adenocarcinoma. The protein encoded by FAT1 plays a crucial role in processes such as cell adhesion, proliferation, and differentiation. This study aims to investigate the expression of FAT1 in lung adenocarcinoma and its relationship with immune infiltration.

METHODS

Gene expression levels and relevant clinical information of 513 lung adenocarcinoma samples and 397 adjacent lung samples were obtained through The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data. The mRNA expression levels of the FAT1 gene in lung adenocarcinoma tissues were analyzed, along with its association with the prognosis of lung adenocarcinoma patients. Pathway enrichment analysis was conducted to explore the signaling pathways regulated by the FAT1 gene. Immunoblotting was used to detect the differential expression of FAT1 in lung epithelial cells and various lung cancer cell lines, while immunohistochemistry was employed to assess FAT1 expression in lung cancer and adjacent tissues.

RESULTS

FAT1 gene mutations were identified in 14% of lung adenocarcinoma patients. TCGA database data revealed significantly higher FAT1 mRNA expression in lung adenocarcinoma tissues compared to adjacent lung tissues. Kaplan-Meier analysis indicated lower survival rates in lung adenocarcinoma patients with higher FAT gene expression. Pathway enrichment analysis suggested the involvement of FAT1 in tumor development pathways, and its expression was closely associated with immune cell infiltration. Immunohistochemical validation demonstrated significantly higher expression of FAT1 in cancer tissues compared to adjacent lung tissues.

CONCLUSIONS

FAT1 mRNA is highly expressed in lung adenocarcinoma tissues, and elevated FAT1 mRNA expression is associated with poor prognosis in lung adenocarcinoma patients. FAT1 may serve as a potential biomarker for lung cancer.

摘要

背景

肺癌是癌症相关死亡的主要原因。非小细胞肺癌(NSCLC)是最常见的病理亚型,腺癌是主要类型。FAT非典型钙黏蛋白1(FAT1)是一种受体样蛋白,在肺腺癌中具有高频率的突变。FAT1编码的蛋白质在细胞黏附、增殖和分化等过程中起关键作用。本研究旨在探讨FAT1在肺腺癌中的表达及其与免疫浸润的关系。

方法

通过癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)数据获得513例肺腺癌样本和397例相邻肺组织样本的基因表达水平及相关临床信息。分析肺腺癌组织中FAT1基因的mRNA表达水平及其与肺腺癌患者预后的关系。进行通路富集分析以探索由FAT1基因调控的信号通路。采用免疫印迹法检测FAT1在肺上皮细胞和各种肺癌细胞系中的差异表达,同时采用免疫组织化学法评估FAT1在肺癌组织和相邻组织中的表达。

结果

14%的肺腺癌患者中检测到FAT1基因突变。TCGA数据库数据显示,与相邻肺组织相比,肺腺癌组织中FAT1 mRNA表达显著更高。Kaplan-Meier分析表明,FAT基因表达较高的肺腺癌患者生存率较低。通路富集分析提示FAT1参与肿瘤发生发展通路,其表达与免疫细胞浸润密切相关。免疫组织化学验证显示,与相邻肺组织相比,癌组织中FAT1表达显著更高。

结论

FAT1 mRNA在肺腺癌组织中高表达,FAT1 mRNA表达升高与肺腺癌患者预后不良相关。FAT1可能作为肺癌的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227a/10918241/915e1ab82a1b/img_5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227a/10918241/0f9d42aafdaa/img_1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227a/10918241/f85a00a11069/img_2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227a/10918241/1461bc940bd2/img_3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227a/10918241/af460cd3c52b/img_4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227a/10918241/915e1ab82a1b/img_5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227a/10918241/0f9d42aafdaa/img_1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227a/10918241/f85a00a11069/img_2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227a/10918241/1461bc940bd2/img_3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227a/10918241/af460cd3c52b/img_4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227a/10918241/915e1ab82a1b/img_5.jpg

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本文引用的文献

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Favorable immune checkpoint inhibitor outcome of patients with melanoma and NSCLC harboring FAT1 mutations.携带FAT1突变的黑色素瘤和非小细胞肺癌患者免疫检查点抑制剂治疗效果良好。
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